BACKGROUND AND AIMS:Atherosclerosis (AS), a critical inflammatory condition of the arteries that leads to cardiovascular diseases, has a complex pathophysiological mechanism involving multifactorial interactions. Endothelial-mesenchymal transition (EndMT) is considered an important factor promoting AS. Laminar shear stress (LSS) has a pivotal function in regulating AS and EndMT processes; however, its specific mechanisms remain unknown. METHODS:We analyzed the transcriptomic and proteomic data of human aortic endothelial cells (HAECs) in static culture and subjected to LSS treatment and identified a key gene, namely sulfiredoxin-1 (SRXN1), closely associated with AS progression. To understand how SRXN1 influences EndMT and AS and the potential underlying mechanisms, we conducted an in vitro flow chamber study with HAECs and an in vivo study with AS model mice. RESULTS:Our results indicated that LSS alleviated oxidized low-density lipoprotein (ox-LDL)-induced EndMT in HAECs. Transcriptome and proteome sequencing analyses showed that SRXN1 functions as a key gene in LSS-treated endothelial cells; moreover, in HAECs, LSS remarkably suppressed ox-LDL-induced inflammation, oxidative stress, and EndMT, and this protective effect was substantially attenuated by SRXN1 knockdown. Additionally, SRXN1 overexpression reversed ox-LDL-induced inflammation and oxidative stress as well as EndMT. In vivo studies revealed that endothelial-specific adeno-associated virus overexpressing SRXN1 (AAV9-SRXN1) administered through the tail vein significantly suppressed aortic plaque development and EndMT in high-fat diet-induced ApoE-/- mice. CONCLUSIONS:Our data demonstrate that LSS through SRXN1 upregulation inhibits oxidative stress and prevents EndMT progression, thereby maintaining endothelial homeostasis and suppressing atherosclerotic progression.

Chemical amplification, spatial confinement and programmable microfluidics collectively enable scalable single-molecule diagnostics.

To monitor neuronal activity with high fidelity, in vitro models must recapitulate not only the cellular composition but also the three-dimensional (3D) microenvironment of the brain. Here, we present an electronic brain biochip that integrates animal-derived decellularized extracellular matrix (dECM) hydrogels with flexible, multichannel electrodes to build a multilayer 3D neural network in which each layer can be independently monitored. Brain dECM hydrogels provide tissue-like biochemical and structural cues that accelerate neurite outgrowth and neural connectivity between layers, enabling the formation of functionally active 3D networks within 3 weeks. We use a low-cost, readily available dECM source from porcine brain tissue, upcycling biological waste into high-value neural scaffolds without compromising biocompatibility. The dECM hydrogels are compatible with both rat primary neurons and hiPSC-derived neurons. Flexible electrode interfaces support real-time, multichannel electrophysiological recording and controlled chemical stimulation. The combination of dECM scaffolding and flexible electrode interfaces supports signal capture throughout the 3D network volume. Functional assays under chemical stimulation reveal bursting and synchronized activity in which all layers participate. By coupling a dECM-based, 3D neural architecture to flexible, multichannel electronics, this work establishes a scalable "electronic organoid" platform for the study of neuronal dynamics and neuropharmacology. Collectively, these advances represent an important step toward artificial brain models that bridge the gap between engineered neural tissues and functional neurobiology.

Iron deficiency anemia (IDA) is a common nutritional deficiency disease caused by iron deficiency. Oral iron supplementation, the simplest and most commonly used iron repletion strategy in the clinic, primarily induces gastrointestinal inflammation, which subsequently elicits complications, including nausea, gastrointestinal bleeding, and constipation. Oral iron supplementation, the most simple and widespread method of iron replenishment in the clinic, primarily causes gastrointestinal inflammation, which, in turn, leads to complications such as nausea, gastrointestinal bleeding, and constipation. Furthermore, gastrointestinal inflammation impedes the absorption of iron, thereby exacerbating anemia. Gold nanoparticles with an inherent anti-inflammatory effect make them a promising weapon for alleviating iron-induced gut inflammation. Herein, we studied the effects of 4,6-diamino-2-pyrimidinethiol (DAPT)-functionalized gold nanoparticles (DAu NPs) on the iron supplementation efficiency and gut inflammation in the IDA model. We discussed the mechanisms of gut microbiota and immune responses on gut inflammation using the 16S rRNA (rRNA) gene sequencing and the polarization of RAW 264.7 cells in vitro. DAu NPs with oral iron supplementation could effectively treat IDA. DAu NPs played a significant role in reshaping gut microbiota, promoting short-chain fatty acid production, and regulating immune responses to reduce inflammation caused by excess iron. In vitro, DAu NPs could inhibit iron-dependent bacteria (Escherichia coli) proliferation while promoting probiotic (Lactobacillus) growth. Oral administration of DAu NPs could regulate M2 polarization of gut macrophages, reduce neutrophil and Th17 cell infiltration, and increase Treg cells recruitment. DAu NPs accumulated primarily in the colon and were excreted via feces, demonstrating excellent biosafety. Our study provides a potential method for the treatment of IDA and other metal element deficiencies.

Gold-nanoparticles-based lateral flow immunoassays (AuNPs-LFIAs) are widely used for point-of-care testing, yet their sensitivity remains fundamentally limited, likely because random antibody orientation on AuNP surfaces restricts Fab accessibility and antigen recognition efficiency. Precise control of antibody orientation is thus critical for maximizing probe activity, yet existing directional conjugation strategies are often multistep, technically complex, and poorly scalable. Here, we report an ultrafast biomimetic mineralization strategy that enables one-step, room-temperature self-assembly of zeolitic imidazolate framework-8 (ZIF-8) with antibodies and dual-ligand AuNPs, producing uniform hybrid nanoprobes within 5 min. ZIF-8 shell preserves the plasmonic properties of AuNPs while simultaneously enhancing colloidal stability and optical signal intensity. Molecular dynamics simulations suggest a two-step orientation model: (i) rapid electrostatic attraction between negatively charged Fc regions and Zn2+ ions initiates nucleation, followed by (ii) Fc-associated interfacial interactions that promote preferential Fc-oriented binding and anisotropic Fc/Fab distribution, thereby enhancing Fab exposure for efficient antigen recognition. This controlled assembly increases Fab accessibility more than 3-fold relative to conventional adsorption or co-precipitation strategies, minimizes nonspecific adsorption, and amplifies signal output. When applied to competitive LFIAs, the oriented nanoprobes enabled ultrasensitive detection of chloramphenicol down to 13 pg/mL, corresponding to approximately 1 order of magnitude higher sensitivity than AuNPs-based LFIA gold standard. By integrating mechanistic insight with operational simplicity, this work establishes a generalizable platform for ultrafast, scalable, and antibody-orientation-controlled nanoprobe fabrication for next-generation LFIAs in food safety, clinical diagnostics, and environmental monitoring.

Lateral flow immunoassay (LFIA) is a vital point-of-care testing (POCT) technique that is widely used for on-site detection and in vitro diagnosis. Many diseases, particularly cardiovascular diseases (CVDs), require the quantitative detection of multiple biomarkers across a broad dynamic range. Recurrent viral infections like COVID-19 elevate CVDs risk, necessitating early warning and prognostic monitoring, especially based on POCT of multiple blood biomarkers of D-dimer, NT-proBNP, and cTnI across a broad range from pg/mL to μg/mL. Traditional LFIAs lack ultrasensitivity and broad-range quantification. We design the surface chemistry-mediated template-free assembly of metal-aggregation-induced emission luminogens (AIEgen) framework@gold nanoparticles (MAF@AuNPs) for developing ultrasensitive and dynamic dual-quantitative LFIA (ddLFIA). The template-free self-assembled MAF@AuNPs have strong fluorescent and plasmonic properties, avoiding complicated synthesis, chemical modifications, and covalent conjugations, thus leading to highly convenient and versatile visual POCT. MAF@AuNPs ddLFIA achieves a normal detection at ng/mL using chromogenic AuNPs and ultrasensitive detection at pg/mL using fluorogenic MAFs, for which the fluorescence signal is 102-103 times more sensitive than the color signal. MAFs and AuNPs are functionally complementary to form a dynamic, broad-range quantification system covering over 5 orders of magnitude, at the same time having a naked eye sensitivity near 1 pg/mL. The visual POCT using MAF@AuNPs ddLFIA aligns well with clinical chemiluminescent assays. MAF@AuNPs ddLFIA perfectly matches ultrasensitive and broad-range multiple biomarker detections for clinical CVDs diagnosis.

The heterogeneity of colorectal cancer (CRC) represents a great challenge in therapy. We integrated multiomics and machine learning, interpreted by SHAP models to provide a clinical rationale, to identify Calcineurin B Homologous Protein 2 (CHP2) as a core candidate, which was further validated via in vitro and zebrafish models. The expression of CHP2 are decreased in CRC, which is associated with a poor prognosis and an immune suppressed “cold” TIME. Functionally, CHP2 overexpression inhibits cell growth and invasion by inducing PANoptosis. Clinically, specific CHP2 expression profiles discriminate patients at high risk that are resistant to standard chemotherapy (e.g., 5-FU) but sensitive to targeted inhibitors. CHP2 is a powerful dual-function biomarker—prognostic for survival and predictive for the response to therapy—that could lead to a personalized approach in treating drug-resistant CRC.

The deformability of cancer cells is a critical indicator of their malignancy, as this mechanical property of cancer cells can reflect various biostructural and biochemical changes such as the cytoskeletons and protein expressions. However, selectively isolating and analyzing cell subpopulations with differing deformability and their associated biological properties remains challenging, especially at high throughput. Here, we introduce a microstructure-assisted spiral microfluidic platform that sorts cancer cells based on their deformability at ultrahigh throughput (>2,000,000 cells min-1) and couples the workflow to real-time, image-based phenotyping of cell parameters. We profile the sorted fractions and investigate a tripartite correlation between the deformability of cancer cells, the expression of proteins in different subpopulations, and the metastatic ability of cancer cells. This tripartite correlation has been confirmed in human breast cancer cell lines with metastatic potential (including MDA-MB-231 cells and BT-549 cells), where these cells are classified into subpopulations based on their deformability. The more deformable subpopulation exhibits increased invasiveness and distinct cytoskeletal remodeling and epithelial-to-mesenchymal transition (EMT)-associated protein signatures. Leveraging these deformability differences, our label-free platform enables high-throughput enrichment of aggressive cancer subpopulations and provides a scalable front end for liquid biopsy workflows. More broadly, deformability-based sorting may support improved analysis of rare metastasis-prone cells and accelerate high-throughput screening for mechano-targeted therapeutic strategies, offering a practical route to integrate cell deformability into precision oncology and therapy.

Neural system injuries remain a major clinical challenge because of the limited regenerative capacity of neural tissues and the formation of inhibitory post-injury microenvironments. Self-assembling peptide hydrogels (SAPHs) have emerged as a highly biomimetic class of materials for neural repair, owing to their nanofibrous architecture, excellent biocompatibility, injectability, and sequence-programmable properties. However, traditional SAPH design largely depends on empirical screening and mechanistic intuition, which limits efficient exploration of the vast peptide sequence space and hinders prediction of the complex relationships among molecular design, supramolecular assembly, material properties, and regenerative outcomes. This review discusses how established SAPH design principles can be reorganized into an AI-assisted design framework for neural regeneration. Within this framework, peptide sequence, assembly behavior, hydrogel performance, and biological responses are integrated as computable and experimentally verifiable design variables. The review summarizes the evolution of SAPH design, outlines AI-assisted workflows covering data construction, feature encoding, predictive modeling, generative design, optimization, and validation, and discusses their potential applications in immunomodulation, vascular reconstruction, neuronal support, Schwann cell or glial regulation, and functional recovery. Key challenges related to data quality, reproducibility, safety, manufacturability, and translation are also considered. Overall, this review provides a design-oriented perspective for advancing SAPHs from empirically optimized materials toward more predictable, iterative, and translationally relevant regenerative platforms.

IntroductionAcinetobacter baumannii is a formidable pathogen renowned for its role in hospital-acquired infections. In recent years, largely due to antibiotic abuse and other reasons, bacteria are frequently exposed to sub-minimum inhibitory concentration (sub-MIC) levels of antibiotics. Accumulating evidence suggests that sub-MIC antibiotic pressure serves as a critical driver of bacterial resistance evolution and virulence adaptation. However, the regulatory mechanisms underlying antibiotic stress adaptation in A. baumannii remains poorly understood. The quorum sensing (QS) system is a key bacterial signaling network that senses population density and coordinates vital physiological functions and environmental adaptations. Targeting QS system to attenuate virulence and resistance represents a promising strategy for combating multi-drug-resistant infections. Nevertheless, the role of systems in regulating antibiotic stress response in A. baumannii has not been elucidated.MethodsIn this study, we used the wild-type (WT) strain of A. baumannii and an isogenic abaI deletion mutant strain (ΔabaI) to investigate the involvement of QS in adaptive responses under meropenem sub-MIC pressure. The analysis was performed by phenotypic experiments such as bacterial biofilm formation and motility detection, transcriptome sequencing (RNA-seq) and qRT-PCR verification.ResultsWe found that under antibiotic pressure, the WT strain developed significantly enhanced resistance, accompanied by increased biofilm formation, surface motility, adherence to and invasion of A549 cells, and pathogenicity in Galleria mellonella. In contrast, the ΔabaI strain showed no significant changes in resistance, motility, host cell adhesion and invasion, or virulence, with all these parameters remaining substantially lower than those of the antibiotic-treated WT. Interestingly, biofilm formation was still significantly enhanced in the ΔabaI strain, suggesting compensatory activation of alternative regulatory mechanisms. Transcriptomic analysis revealed that sub-MIC meropenem triggered extensive gene expression changes in both the WT and ΔabaI strains. In the WT, differentially expressed genes were enriched in pathways including quorum sensing, biofilm formation, ABC transporters, and two-component systems. In contrast, the ΔabaI mutant exhibited distinct transcriptional profiles, with enrichment in Δ-lactam resistance, aromatic amino acid biosynthesis, and metabolite transport. The expression trends of key virulence- and resistance-associated genes were further validated by qRT-PCR, confirming the reliability of the RNA-seq data.DiscussionOur study underscores the potential of targeting the QS system to mitigate antibiotic-driven adaptation and provides a strategic basis for controlling multidrug-resistant A. baumannii infections.

Immune checkpoint blockade has revolutionized oncology, yet low response rates and acquired resistance-often driven by inadequate Programmed death-ligand 1 (PD-L1) suppression-remain significant barriers. While degradation-based proteolysis-targeting chimeras offer a promising alternative to traditional antibodies, targeting the intracellular and transcriptional drivers of checkpoint expression remains a challenge. We report a programmable, tumor-responsive DNA hydrogel platform, synthesized via rolling circle amplification, designed for the comprehensive, dual-mode modulation of PD-L1. This modular nucleic acid framework codelivers polyvalent aptamer-based lysosome-targeting chimeras (LYTAC mimics) to induce extracellular PD-L1 degradation and siSMARCAL1 to silence the chromatin-remodeling-driven transcriptional activation of PD-L1. By integrating localized, sequential release within the tumor microenvironment, this system achieves a synergistic "degrade-and-silence" effect that effectively dismantles PD-1/PD-L1-mediated immunosuppression while concurrently triggering immunogenic cell death. In murine melanoma models, the hydrogel significantly suppressed primary tumor growth and prevented postoperative recurrence, eliciting a robust and durable systemic antitumor immune response. Our findings establish a versatile, DNA-based materials strategy for programmable protein degradation and multilevel checkpoint modulation, offering a generalizable approach for enhancing the efficacy of cancer immunotherapy.

Induction of broad and potent immune responses by vaccines is required to prevent infection from highly variable pathogens like human immunodeficiency viruses (HIV), influenza viruses (IFV) and SARS-CoV-2. The extensive genetic diversity of HIV underscores the need for vaccines capable of eliciting broadly neutralizing antibodies (bnAbs). However, induction of such bnAbs has not been achieved by the current HIV vaccine candidates. To enhance the neutralization breadth, we developed a new vaccine delivery platform consisting of the TLR7/8-activating nanoparticles (TNP) using the microfluidic technology. We then conjugated the native-like HIV-1 envelope (Env) glycoprotein trimers on the TNP surface to generate an HIV nanovaccine (Env_TNP). Env_TNP enhances antigen accumulation in lymph nodes and dendritic cell (DC) activation, increases expression of major histocompatibility complex class II (MHC II) on the DC surface and elicits strong B cell proliferation in mice. Furthermore, immunization in guinea pigs with Env_TNP induces significantly higher titers of neutralizing antibodies (nAbs) and increases the neutralization breadth against diverse HIV-1 strains compared to Env with adjuvant BFA03 or Env alone. These findings demonstrate that the newly developed Env_TNP nanovaccine can enhance the potency and breadth of nAb responses by presenting the Env trimers as large nanoparticles and utilizing the immunostimulatory properties of the TLR7/8 agonist 1 to improve antigen presentation and B cell activation. Overall, this new vaccine delivery platform has strong potentials to improve the immunogenicity of HIV vaccines and can be applied to other protein-based vaccines.

The clinical potential of cyclic dinucleotides (CDNs) as potent agonists of the stimulator of interferon gene (STING) has been hampered by the lack of robust delivery systems. While lipid nanoparticles (LNPs) excel with large nucleic acids, they are unsuitable for delivering small, zwitterionic and highly hydrophilic CDNs. Here, we find that the tertiary amine oxide lipid (AOL) promotes stable encapsulation of CDNs into LNP through enhanced hydrogen bonding and electrostatic interactions, resulting in ultra-high encapsulation efficiency of 86.8%. Compared to cationic liposomes, AOL-incorporating LNP exhibits superior tumor penetration and cytosolic cargo delivery, eliciting broad and potent intratumoral STING activation. In line with growing emphasis on combination therapy in oncology, we further incorporate lipidated mitoxantrone in the LNP as an inducer of immunogenic cell death to enhance tumor antigen presentation and STING-driven immunotherapy. The obtained LNP provokes potent immunostimulatory and antitumor effects in multiple challenging animal models, including triple-negative breast cancer, pancreatic cancer and melanoma.

Chitosan-based mesenchymal stem cell (MSC) therapy strategies present a promising approach for peripheral nerves repair following injury. However, the therapeutic efficacy of MSCs is significantly hindered by low cell viability and suboptimal retention at the implantation site. Herein, a bio-orthogonal strategy that covalently integrates MSCs with chitosan for nerve regeneration is presented. In vitro analysis revealed covalent combination enhanced adhesion and survival of MSCs on chitosan scaffolds via phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) signaling pathway. Quantitative proteomics confirmed that these MSCs enhance the secretion of key neurotrophic factors for neuroregeneration. In vivo investigations utilizing a nerve crush injury model demonstrated that bio-orthogonal-mediated MSC therapy markedly improves cell retention at the lesion site. Furthermore, this innovative strategy actively modulates the immune microenvironment, accelerates Wallerian degeneration, promotes angiogenesis, and remodels the extracellular matrix, thereby expediting repair processes following peripheral nerve injury. Specifically, further evaluation utilizing a 10 mm sciatic nerve transection model demonstrated that the bio-orthogonal strategy significantly enhanced the therapeutic efficacy of MSCs. Collectively, the approach developed in this study provides a simple, efficient, and translatable strategy for augmenting MSC-mediated peripheral nerve repair. This work lays a solid theoretical foundation for the future clinical application of chitosan-MSC composite materials in neuroregenerative medicine.

Gold nanoparticles (GNPs) are promising antimicrobial agents due to their high bactericidal efficiency and low propensity for inducing drug resistance. The rational design of GNPs with improved efficiency, desired spectrum, and low toxicity requires a deep understanding of their antimicrobial mechanisms. However, the inherent flexibility and diversity of molecular modifications achievable on GNPs render their antibacterial mechanisms significantly more complex than those of traditional molecular antimicrobial drugs. This complexity poses substantial challenges for elucidation using existing techniques. In this work, we employed single-cell physiology profiling for the first time to investigate the bactericidal dynamics of GNPs. Utilizing the previously developed GNP, Au-DAPT, against the gram-negative model organism Escherichia coli, this approach revealed a three-step bactericidal dynamic characterized by growth rate-independent morphological perturbation and division-dependent cell killing. This finding provides a valuable foundation and specific guidance for future molecular-level investigations aimed at identifying the precise targets of Au-DAPT. Furthermore, this work establishes a research paradigm for studying antimicrobial agents with complex mechanisms.

Ultrathin conductive hydrogels provide conformal and stable contact for flexible bioelectronics, which is critical for achieving the low impedance necessary for high-quality electrophysiological signal acquisition. However, their low modulus has made these hydrogel devices difficult to fabricate and handle. To overcome this, we present an on-demand formation strategy for creating ready-to-use, ultrathin (down to 1 micrometer) hydrogel-based bioelectronics that combine tissue-like softness with ready-to-use functionality. By using cross-linked electrospun polyvinyl alcohol (PVA) fiber mats, we produce liquid metal-patterned hydrogel tattoos (LMHTs). These devices transform from easy-to-handle dry films into adhesive, conformal hydrogel interfaces upon hydration. The resulting LMHTs are ultralight (0.9 milligrams per square centimeter), exhibit ultralow skin contact impedance (1.2 kilohms at 1 kilohertz), and show outstanding biocompatibility. We demonstrate their utility in diverse on-skin and implantable applications, including electrocardiogram recording, multichannel electromyogram mapping, neuromuscular electrical stimulation, and in vivo cardiac monitoring on a beating rat heart. This work offers a scalable and practical approach for generating high-performance, ultrathin hydrogel bioelectronics.

Abstract Point-of-care testing (POCT) plays a crucial role in both clinical- and home-based diagnostics. Integrated POCT systems that combine nucleic acid extraction with detection provide significant advantages, including portable operation, rapid processing, and high sensitivity. In this work, we present a fully automated and integrated nucleic acid detection system based on microfluidic chips with a surface-engraved rotary piston (SERP), which incorporates all of the liquid channels on the surface of one valve. This design consists of only three parts: the chip, the rubber sealing ring, and the rotary valve containing microfluidic channels, allowing the sequential connection of reaction chambers to facilitate nucleic acid extraction, recombinase polymerase amplification (RPA), and clustered regularly interspaced short palindromic repeats (CRISPR) into a single chip. Our chip consists of only three components, can be fabricated directly by 3D printing, and features a simple structure with a compact size. This platform was employed for the detection of human papillomavirus (HPV16) DNA, achieving a limit of detection (LOD) as low as 60 copies/mL. This result underscores the potential of the SERP as a rapid, cost-effective, and modular solution for POCT applications.

Biosensors based on electrolyte-gated organic field-effect transistors (EGOFETs) have attracted considerable attention due to their advantages, including low cost, inherent signal amplification, and low-voltage operation. A critical step influencing sensing performance is the integration of specific receptors onto the device surface. Among various strategies, the covalent immobilization of biorecognition elements onto gold surfaces via thiol chemistry is one of the most widely used approaches. In this study, we report the optimization of a mixed self-assembled monolayer (SAM) composed of 11-mercaptoundecanoic acid (11-MUA) and 3-mercaptopropionic acid (3-MPA) for label-free detection of human IgG using EGOFETs. The quality of the SAM was systematically modulated by varying the total concentration from 10 to 400 mM and characterized using X-ray Photoelectron Spectroscopy (XPS), Electrochemical Impedance Spectroscopy (EIS), Cyclic Voltammetry (CV), and Atomic Force Microscopy (AFM). The results revealed that a concentration of 50 mM yielded a densely packed and well-ordered monolayer. After covalent immobilization of anti-IgG antibodies via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) chemistry and subsequent blocking with ethanolamine and bovine serum albumin (BSA), the functionalized gate electrodes were integrated into poly(3-hexylthiophene) (P3HT)-based EGOFETs. Electrical measurements demonstrated that EGOFET biosensors functionalized with the 50 mM SAM achieved optimal sensing performance. The devices exhibited a highly linear response (R2 = 0.998) over a wide concentration range from 1 fM to 10 nM, with a LOD of 2.82 fM, and showed excellent selectivity against non-target immunoglobulins A and M (IgA and IgM). This SAM concentration optimization strategy provides a versatile approach for engineering high-performance EGOFET biosensors, with potential applicability to a broad range of disease biomarkers.

Chemical aggregates span multiple scales, from single molecules to nanoscale assemblies and macroscopic systems, exhibiting diverse functionalities towards biomedical purposes. The development of multiscale aggregation materials provides a powerful strategy to enable innovative solutions for treating diseases and performing bioanalysis. In this review, we summarize our recent progress in leveraging aggregation materials for antimicrobial therapy, bioanalysis, and drug delivery from a multiscale perspective. We highlight the discovery of small molecules, microfluidics-assembled or chemically synthesized nanoscale aggregation materials, and mesoscale biological aggregation interfaces for a broad range of biomedical applications. We also discuss current challenges in developing aggregation materials and explore directions for practical translations.